Influenza infection (also referred to as “influenza” or “the flu”) is a highly contagious disease with the potential to be devastating both in developing and developed countries. Influenza rapidly spreads in seasonal epidemics affecting 5-15% of the population and the burden on health care costs and lost productivity are extensive (World Healthcare Organization (WHO)).
There are three genera of influenza virus (types A, B and C) responsible for infectious pathologies in humans and animals. The type A and type B viruses are the agents responsible for the influenza seasonal epidemics (type A and B) and pandemics (type A) observed in humans.
Influenza A viruses can be classified into influenza virus subtypes based on variations in antigenic regions of two genes that encode the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) which are required for viral attachment and cellular release, respectively. Currently, sixteen subtypes of HA (H1-H16) and nine NA (N1-N9) antigenic variants are known in influenza A virus. Only some of the influenza A subtypes (i.e. H1N1, H1N2 and H3N2) circulate among people, but all combinations of the 16 HA and 9 NA subtypes have been identified in animals, in particular in avian species. Animals infected with influenza A often act as a reservoir for the influenza viruses and certain subtypes have been shown to cross the species barrier to humans, such as the highly pathogenic influenza A strain H5N1.
The influenza type B virus strains are only known to infect humans and seals. Comparison of the sequence divergence among genes of viruses belonging to type A, B, and C virus suggests that, in man, type B viruses evolve slower than type A viruses and faster than type C viruses. It appears that type B viruses mutate at a rate that is two- to three times lower than type A. Two genetically and antigenically distinct lineages of influenza B virus are circulating in humans, as represented by the B/Yamagata/16/88 (also referred to as B/Yamagata) and B/Victoria/2/87 (B/Victoria). Although the spectrum of disease caused by influenza B viruses is generally milder than that caused by influenza A viruses, severe illness requiring hospitalization is still frequently observed with influenza B infection.
Current approaches to dealing with annual influenza epidemics include annual vaccination. However, because circulating influenza viruses in humans are subject to frequent antigenic changes, annual adaptation of the influenza vaccine formulation is required to ensure the closest possible match between the influenza vaccine strains and the circulating influenza strains. In addition, antiviral drugs, such as oseltamivir (Tamiflu®) are used for prevention and treatment of influenza infection. The number of influenza virus strains showing resistance against antiviral drugs, such as oseltamivir is, however, increasing.
An alternative approach is the development of antibody-based prophylactic or therapeutic treatments to neutralize various seasonal and pandemic influenza viruses. Thus, several antibodies capable of neutralizing influenza A and/or B viruses have been described (e.g. WO2008/028946 and WO2013/007770).
In view of the severity of the respiratory illness caused by influenza viruses, as well has the high economic impact of the seasonal epidemics, and the continuing risk for pandemics, there is an ongoing need for new effective means for the prevention and treatment of influenza infections.